Objective  To investigate the impact of insulin resistance (IR) on pregnancy outcomes in patients with unexplained recurrent implantation failure (URIF) and evaluate the potential therapeutic value of metformin.

Methods  A retrospective analysis was performed on the clinical data of 335 patients with URIF who underwent in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatment at Liuzhou Municipal Maternity and Child Health Care Hospital and Guangxi Reproductive Medical Center of the First Affiliated Hospital of Guangxi Medical University between January 2019 and February 2022. Patients were stratified into metformin and control groups according to whether they received metformin treatment, with further subdivision based on homeostasis model assessment of IR (HOMA-IR) index into IR and non-IR subgroups. The primary outcome was live birth rate; the secondary outcomes included clinical pregnancy rate and early pregnancy loss rate. Multivariate logistic regression analysis was used to identify the risk factors affecting pregnancy outcomes in URIF patients.

Results  The IR group showed significantly higher early pregnancy loss rate than non-IR group (24.11% vs. 13.77%, P < 0.05), while there were no statistically significant differences in the live birth rate and clinical pregnancy rate between the two groups (30.43% vs. 26.79%, P=0.526; 42.75% vs. 38.39%, P=0.486). After adjusting for confounding factors, IR remained an independent risk factor for early pregnancy loss (OR= 1.385, 95% CI: 1.035-2.508, P < 0.05); metformin treatment reduced the early pregnancy loss rate in the IR group (15.63% vs. 30.36%, P < 0.05).

Conclusion  IR is an independent risk factor for early pregnancy loss in URIF patients. Metformin may improve pregnancy maintenance by ameliorating IR, though its long-term effects on live birth require further validation.